St. Louis encephalitis (SLE) is of concern in many areas of the US, with recent outbreaks or isolated cases in 10 states. Although this virus and its mosquito vectors have been the subject of much research, there are still many unanswered questions about the system. In particular, the factors which lead to an epidemic are not well understood. The proposed research will use mathematical models to integrate available information on the SLE virus-Culex nigripalpus cycle in Florida and examine the factors influencing transmission and epidemics. A basic virus transmission model with two host types and one vector species will be expanded to consider questions about SLE transmission in Florida. Four main topics will be addressed: age-related susceptibility differences and population dynamics of avian hosts; host preferences and seasonal changes in preferences in the mosquito vector; the meteorological factors affecting Cx. nigripalpus population dynamics; and the potential role of secondary vectors in SLE epidemiology. These factors will be added to the model individually and in combination, to determine the effect of each on SLE epidemiology. Formal sensitivity analysis will be used to identify how uncertainties in parameter estimates affect uncertainty in the likelihood of epidemics and the prevalence of virus in the wild hosts. Field and laboratory experiments will be used in parameter estimation and in testing hypotheses generated by the models. Comparisons of model output with data from ongoing virus surveillance projects will be used for model validation. The final model will be used to explore potential indicators of epidemics and intervention strategies.